RANDOMIZED DOUBLE-BLIND PROSPECTIVE TRIAL TO EVALUATE THE EFFECTS OF SARGRAMOSTIM VERSUS PLACEBO IN A MODERATE-DOSE FLUOROURACIL, DOXORUBICIN, AND CYCLOPHOSPHAMIDE ADJUVANT CHEMOTHERAPY PROGRAM FOR STAGE-II AND STAGE-III BREAST-CANCER

Purpose: To determine the effects of sargramostim (recombinant human g ranulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) on the i ncidence, duration, and complications of myelosuppression after modera te-dose fluorouracil, doxorubicin, cyclophosphamide (FAG) adjuvant che motherapy in patients with node-positive breast cancer. Patients and M ethods: In this randomized, double-blind, placebo-controlled study, 14 2 women with stage II and III breast cancer were to receive four 21-da y cycles of chemotherapy that consisted of fluorouracil 600 mg/m(2) in travenously (IV), doxorubicin 60 mg/m(2) IV, and cyclophosphamide 750 mg/m(2) IV on day 1, followed by placebo or GM-CSF 250 mu g/m(2)/d dai ly subcutaneously (SC) on days 3 through 15. All patients received pro phylactic ciprofloxacin by mouth when the absolute neutrophil count (A NC) was less than 1,000/mu L. Results: Eighty-six percent of GM-CSF pa tients (n=62) and 96% of placebo patients (n=69) completed four assess able cycles of treatment on study. Overall, the median duration of sev ere neutropenia (ANC <500/mu L) was 2.8 days with GM-CSF and 6.8 days with placebo (P <.001); the duration of ANC less than 1,000/mu L was 6 .0 versus 9.1 days, respectively (P <.001). Hospitalizations for febri le neutropenia were uncommon in either group: GM-CSF, six; placebo, ei ght, The only other difference in hematologic toxicity was grade 3/4 t hrombocytopenia observed with greater frequency in GM-CSF patients tha n placebo patients in cycles 3 and 4. GM-CSF increased mean the FAC do se intensity among patients who completed two or more cycles (P <.001) . GM-CSF was generally well tolerated and associated with more injecti on-sire reactions, but less mucositis than placebo. There were no deat hs on study. Conclusion: GM-CSF significantly enhanced ANC recovery af ter FAC chemotherapy; it decreased the incidence and duration of assoc iated neutropenia and moderately increased the dose-intensity of adjuv ant chemotherapy. Whether these effects will ultimately translate into improved long-term outcome remains to be determined. (C) 1996 by Amer ican Society of Clinical Oncology.